tbuckley/cabot-search huggingface dataset:
Barriers to effective childhood cancer control in Kenya (BECK) study, 2019-2020: A mixed methods study in a national tertiary facility and 10 regional cancer treatment centers.
Authors: Valerian Mwenda, Alfred Karagu, Jessie Nyokabi Githanga, Mary Nyangasi
Journal: Journal of Clinical Oncology (2022)

10018 Background: Globally, 80,000 children die from cancer annually; 80% in low- and middle-income countries (LMICs). Childhood cancer cure is possible in more than 80% of cases, in all economic settings. This study aimed to identify barriers to effective management of childhood cancers in Kenya, for program and policy intervention. Methods: We reviewed childhood cancer cases diagnosed at Kenyatta National Hospital in the period 2015-2019. We also assessed capacity of ten recently established regional cancer centres for childhood cancer diagnosis and treatment. We conducted focused group discussions among childhood cancer survivors’ caregivers and key informant interviews among childhood cancer specialists and policy makers from the Ministry of Health and the National Cancer Institute of Kenya. We estimated diagnostic delays, mapped service availability and deductively summarized the qualitative data into main themes. Results: We abstracted 1,764 cases; median age 6 years (IQR 9); 1013 (57.5%) were male. Most affected age group was 0-4 years (47.3%). Most common cancer types were retinoblastoma (23.3%), nephroblasoma (10.4%) and acute lymphoblastic leukaemia 10.3%). Cases managed at KNH decreased between 2015 and 2017, and then recovered. The median total delay (symptoms onset to treatment initiation) was 32 days (range 0-3666). Regional cancer centres lacked specialized workforce for childhood cancer care. Caregivers identified inadequate cover by National Health Insurance and disorganized care process as major challenges. At health system and policy level, low awareness, fragmented referral systems and in-effective policy implementation are major challenges to childhood cancer control. Conclusions: Increasing number of specialized personnel, creation of a differentiated financing package for childhood cancer and restructuring of referral and the care process can improve childhood cancer outcomes in Kenya.
Diagnostic performance of mixed targeted prostate biopsy approaches using micro-ultrasound and MRI-fusion biopsies
Authors: D. Maffei, C. Saitta, P.P. Avolio, M. Paciotti, N. Frego, V. Fasulo, P. Diana, M. Lazzeri, R. Hurle, A.R. Saita, G.F. Guazzoni, P. Casale, N.M. Buffi, G. Lughezzani
Journal: European Urology (2022)
Inflammatory signals hidden in the CBC are detectable prior to durvalumab-induced pneumonitis.
Authors: Kathryn DeCarli, Rebecca Masel, Adam J Olszewski, Neel Belani, Paul Koffer, Christopher G. Azzoli
Journal: Journal of Clinical Oncology (2022)

e21116 Background: For patients with unresectable stage III non-small cell lung cancer (NSCLC), chemoradiation followed by 1 year of durvalumab is standard of care. Treatment-induced pneumonitis can be life-threatening. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune inflammation index (SII, defined as platelet x neutrophil / lymphocyte counts) are calculated from the CBC and have been studied as inflammatory biomarkers in a variety of settings. This study assessed trends in these indices among patients treated for stage III NSCLC. Methods: We reviewed medical records of adults with stage III NSCLC who completed chemoradiation and durvalumab from 1/2017 to 9/2021 as part of routine care. Patients who developed non-pneumonitis immune toxicity were excluded. NLR, PLR and SII were calculated at dates of first and last radiation dose and first durvalumab dose. For patients who developed pneumonitis, indices were also calculated at each of 8 weeks leading up to pneumonitis onset, defined as the first diagnostic CT scan and graded as 1-5 based on CTCAE criteria. Indices were compared between the pneumonitis and no pneumonitis group using rank-sum test. P values &lt; 0.05 were considered statistically significant without adjustment for multiple testing. The slope of linear trend for each index was examined via log-gamma generalized linear regression model using a random intercept for each patient and robust standard error. Results: Of 65 patients who received chemoradiation followed by durvalumab, 2 were excluded because they were on clinical trial and 28 were excluded for non-pneumonitis immune toxicity. Among the 35 patients eligible for analysis, median age was 67 years; 20 (57%) were female; 6 (17%) were current smokers; 15 (43%) had COPD; and 17 (49%) developed pneumonitis (2 G1; 11 G2; 3 G3; 0 G4; 1 G5). In the pneumonitis group, NLR (p = 0.022), PLR (p = 0.007) and SII (p = 0.001) showed a statistically significant linear increase in the 5 weeks preceding pneumonitis onset. There were no differences in clinical characteristics, SII, NLR or PLR between the pneumonitis and no pneumonitis groups at the 3 time points examined. Conclusions: In this exploratory analysis, patients who developed pneumonitis showed a linear increase in inflammatory indices for 5 weeks before pneumonitis onset, suggesting information hidden in routine blood tests can anticipate development of a life-threatening complication. Our hypothesis-generating study will need validation in a larger prospective analysis with a control group. Future directions may also include examination of selected acute phase reactants or cytokines.
Cold-sensitive ventromedial hypothalamic neurons control homeostatic thermogenesis and social interaction-associated hyperthermia
Authors: Chenzhang Feng, Ying Wang, Xi Zha, Huateng Cao, Shajin Huang, Dongdong Cao, Kaiwei Zhang, Tianyuan Xie, Xiaohong Xu, Zhifeng Liang, Zhe Zhang
Journal: Cell Metabolism (2022)
Bortezomib in PTEN-deficient patients with advanced intrahepatic cholangiocarcinoma: An open-label, prospective, phase II trial.
Authors: Zhen-gang Yuan
Journal: Journal of Clinical Oncology (2022)

4092 Background: Intrahepatic cholangiocarcinoma (ICC) is the second-most common primary liver malignancy after hepatocellular carcinoma. Prognosis of cholangiocarcinoma is poor and therapy options are limited. Bortezomib in unselected patients with BTC has been failed in previous clinical trial. Our previous research dedicates that PTEN-deficient facilitates sensitivity to proteasome inhibition in intrahepatic cholangiocarcinoma. In this open-label，prospective，phase II trial, we explore the efficacy and safety of bortezomib in PTEN-deficient advanced intrahepatic cholangiocarcinoma patients who have progressed during Gemcitabine based treatment. Methods: Between August 1, 2017, and July 31, 2021, A total of 130 patients were under went PTEN immunohistochemical staining for screening and 15 patients enrolled. Patients with PTEN-deficient advanced intrahepatic cholangiocarcinoma who had progressed after GC/Gemox therapies received bortezomib 1.3 mg/m2 days 1, 4, 8, and 11 of a 21-day cycle. The primary endpoint was objective response rate according to Response Evaluation Criteria in Solid Tumors v1.1. Results: The overall response rate was 23.1% (3/13) and disease control rate was 53.8% (7/13). The Median time of follow up was 4.2 months (95% CI: 0.7̃17.2 months). median progression-free survival was 2.3 months and the median overall survival was 9.6 months. Adverse events of any grade were reported in 14 patients. Thrombopenia was the most common toxicity. Conclusions: Bortezomib provided an encouraging objective response and disease control as second-line therapy for PTEN-deficient Patients with advanced intrahepatic cholangiocarcinoma, and improving the overall survival to 9.6 months. Bortezomib would be a promising treatment option in PTEN-deficient selected patients.
Some plant metabolites from Petasítes sp. and their effect on cancer cells motility in vitro.
Authors: Sofia V. Timofeeva, Oleg I. Kit, Svetlana Yu Filippova, Anastasia O. Sitkovskaya, Irina V. Mezhevova, Nadezhda V. Gnennaya, Tatiana V. Shamova, Inna A. Novikova, Yaroslav S. Enin, Oleg N. Burov, Elena Yu Zlatnik, Anna P. Menshenina, Tatiana I. Moiseenko, Ekaterina V. Verenikina, Oksana E. Zhenilo, Yuriy A. Poryvaev, Tatiana Yu. Myagkova, Viktoria V. Pozdnyakova, Meri L. Adamyan
Journal: Journal of Clinical Oncology (2022)

e15077 Background: Plant metabolites are traditionally a valuable source of anticancer drugs. The huge variety of molecular structures found in plants makes it possible to isolate substances that possess not only antimitotic, but also anti-migratory properties on cancer cells. The objective of this study was to evaluate the anti-migratory activity of selected metabolites from Petasítes sp. plants. Methods: Cells of cancer cell cultures PC3 (prostate cancer), A431 (skin cancer), CaCo-2 (colorectal cancer), HeLa (cervical cancer) and T98G (glioma) were seeded in an amount of 15*10 4 cells per well of a 24-well plate (Biofil, China) in DMEM medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA). After cell adhesion the test substances at a concentration of 40 µM were added, and a wound healing assay was performed according to the standard procedure. The study included the following metabolites: 1) substance 1 (S1) - 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one; 2) substance 2 (S2) - 5-(hydroxymethyl)furan-2-carbaldehyde; 3) substance 3 (S3) - corynan. The wound area was measured using a Lionheart FX imager (BioTek, USA) at starting time point and after 48 hours of cultivation. Data are presented as mean±95% confidence interval (n = 12). Results: The studied cultures were found to be differently sensitive to the tested substances. Cells of CaCo-2 and PC3 cultures did not demonstrate a significant decrease in mobility, as the degree of scratch overgrowth did not decrease compared to the control without the addition of substances (α = 0.05, df = 22) in all variants of the experiment. However, the A431 skin cancer culture showed reduced motility in all three trials compared to the no-substance control. Namely, the wound area reduction was 81.52 ± 9.6% in the control, 63.77 ± 8.4% in S1 variant, 62.42 ± 6.3% in S2 variant, and 12.05 ± 7.1% in S3 variant. Also, a slowdown in cell motility was observed in HeLa (28.92±5.1% compared to 37.0±6.3% in control) and T98G cells (82.41±9.1% compared to with 97.35±1.9% in control) when incubated with S1. Taking into account the correction for multiple comparisons, only the results for A431 turned out to be significant, but the results obtained for HeLa and T98G cultures were not significant at a corrected significance level (α = 0.003, df = 22). Conclusions: Further studies of 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one anti-migratory properties are of particular interest, since it showed promising results in three of the five studied cancer cell cultures.
Repurposing HDAC and mTOR inhibitors for pancreatic cancer.
Authors: Mitch Biermann, Cynthia Quintero, Paige Ferguson, Nirakar Rajbhandari, Donglim Esther Park, Hitendra Patel, Tannishtha Reya
Journal: Journal of Clinical Oncology (2022)

e16234 Background: Pancreatic ductal adenocarcinoma (PDAC) will be the second leading cause of cancer death by 2030 through early onset dedifferentiation and metastasis that results in limited treatments. FDA-approved targeted therapies–including proteasome, mitogen-activated protein kinase (MEK), histone deacetylase (HDAC), and mammalian target of rapamycin (mTOR) inhibitors–have shown preclinical benefit but failed in clinic. However, combination targeted therapy has been largely unexplored in clinical trials. We hypothesized based on prior drug screening efforts in the lab on aggressive subtypes of pancreatic cancer that combinations of these targeted therapies could be synergistically active in preclinical PDAC models. Methods: We optimized combinations of proteasome, MEK, mTOR, and HDAC inhibitors by performing cell viability experiments in human PDAC lines in 2D and 3D cell culture conditions in vitro. Optimized drug combinations from these experiments were then trialed in two different in vivo animal models–human FG xenografts in immunocompromised mice (NSG) and spontaneous primary PDAC tumors from transgenic pancreatic-specific Kras-overexpressing, P53-deficient mice (KPC). RNA-sequencing and Seahorse metabolic assays were utilized to analyze molecular mechanisms of drug synergy. Dedifferentiation was assessed by histology of KPC tumors. Results: The HDAC inhibitor Panobinostat and mTOR inhibitor Everolimus synergistically killed human pancreatic cancer cell lines grown in 2D and 3D cell culture in vitro. Synergy was highest at low concentrations of Panobinostat. In vivo, low-dose Panobinostat and Everolimus synergistically blocked growth of human FG xenografts in NSG mice. In vivo synergy of low-dose Panobinostat and Everolimus was highest in the KPC mouse model, where only combination therapy could significantly reduce tumor growth, stall dedifferentiation, and improve survival. Mechanistically, RNA-sequencing of Panobinostat/Everolimus-treated FG cells revealed that Panobinostat increased tumor suppressor genes opposing dedifferentiation such as p21, EGR1, and CCN2. Everolimus complemented Panobinostat by decreasing expression of enzymes metabolizing acetyl groups such as fatty acid synthase, stearoyl-CoA desaturase, and sterol response element binding factors. Functionally, Everolimus’ activity to reduce oxidative consumption increased histone acetylation specifically in the presence of Panobinostat. Conclusions: A combination of FDA-approved, targeted oral therapies (low-dose Panobinostat/Everolimus) is synergistically active in preclinical models of pancreatic cancer in vitro and in vivo. mTOR inhibitors create drug synergy by specifically increasing histone acetylation in HDAC inhibitor-treated cells by reversing HDAC inhibitor de-repression of acetyl/oxidative metabolism, illustrating a novel connection between cancer epigenetics and metabolism.
Treatment and outcome of patients with high-grade advanced ovarian cancer (AOC): Real-world data in Germany (QS Ovar of the AGO Study Group).
Authors: Sven Mahner, Philipp Harter, Andreas Du Bois, Felix Hilpert, Markus Kerkmann, Jalid Sehouli, Nikolaus de Gregorio, Lars Ch. Hanker, Florian Heitz, Frederik Marmé, Linn Lena Woelber, Laura Holtmann, Gabriele Elser, Jacobus Pfisterer
Journal: Journal of Clinical Oncology (2022)

e17613 Background: Outcome of patients with ovarian cancer depends largely on treatment quality and expertise of treating physicians and centers. To assess treatment reality and quality in Germany, we initiated a nationwide quality assurance program. Methods: All German hospitals treating patients with ovarian cancer were asked to document their patients with primary diagnosis of epithelial ovarian cancer in the third quarters of 2012 and 2016. Details of tumor, treatment and outcome were documented in a central database. The current analysis focuses on patients with high-grade AOC stage III/IV. Results: In total, 1010 patients with high-grade AOC were documented. This represents 63% of all patients diagnosed with AOC in Germany in these periods. Median age was 65 years. The majority (774/1010 - 76.6%) were diagnosed with stage III disease and 947/1010 (93.8%) had serous, 34 (3.4%) endometrioid and 29 (2.9%) clear cell histology. 915/1010 (90.6%) had primary cytoreductive surgery. Complete resection was achieved in 434/915 (47.4%) at primary surgery and in 54/95 (56.8%) at interval debulking surgery. Median PFS and OS in patients with primary surgery and complete resection was 29.7 months and 63.1 months compared to 16.8 months and 30.7 months in patients with residual disease (HR PFS 0.46 95% CI 0.22-0.54 HR OS: 0.38 95% CI 0.31-0.45). In patients with neoadjuvant chemotherapy and interval debulking, median PFS and OS were 24.3 and 50.7 months with complete resection, compared to 15.4 and 33.9 months with residual disease (HR PFS 0.61 95% CI 0.38-0.95 HR OS: 0.48 95% CI 0.28-0.83). First-line chemotherapy was carboplatin/paclitaxel (TC) in 919/1010 (91%) of the patients, 627 (62%) also received bevacizumab (TCB) and 544 of these (87%) also received maintenance therapy. Median PFS and OS in patients with TCB was 23.3 months and 46.2 months and 18.5 months and 39.0 months in patients treated with TC (p = 0.049: HR 0.85, 95% CI 0.72-1.00 and p = 0.012: HR 0.79, 95% CI 0.65-0.95). The rate of complete tumor resection at surgery as well as the use of bevacizumab increased between the two periods. Conclusions: Based on this representative cohort of patients with advanced ovarian cancer in Germany, the majority of patients is treated with primary surgery followed by carboplatin/paclitaxel and bevacizumab. Patient outcome regarding PFS and OS was best when complete tumor resection was achieved at primary surgery and patients received combination chemotherapy with maintenance treatment. Supported by Roche, Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Essex.
Safety and efficacy of personalized LND vs. ePLND during radical prostatectomy. Personalympca: A randomized phase II study
Authors: M. Ramírez-Backhaus, F. Claps, Á. Gómez-Ferrer, A. Collado Serra, A. Calatrava Fons, J.L. Marenco, J.M. Mascaros, J. Rubio-Briones
Journal: European Urology (2022)
Role of Matrix assisted Laser Desorption/ionization (MALDI)- Mass Spectrometry Imaging (MSI): A novel tool to study bioenergetic signature in kidney cancer
Authors: H. Garg, A. Pamreddy, L. Hejazi, D. Montemayor, Y. Ding, M.A. Venkatachalam, K. Sharma, D. Kaushik
Journal: European Urology (2022)
Clinical features and outcomes of non-pulmonary unifocal adult Langerhans cell histiocytosis
Authors: Marie Hu, Gaurav Goyal, Jithma P. Abeykoon, Aldo A. Acosta-Medina, Gordan J. Ruan, Jason R. Young, Aishwarya Ravindran, N. Nora Bennani, Mithun V. Shah, Robert Vassallo, Jay H. Ryu, Caroline J. Davidge-Pitts, Matthew J. Koster, W. Oliver Tobin, Julio C. Sartori-Valinotti, Karen L. Rech, Ronald S. Go
Journal: Blood Cancer Journal (2022)
Total metabolic tumor volume on 18F-fluorodeoxyglucose-positron emission tomography ([18F]-FDG-PET) scan: A potential prognostic factor in extensive-stage small cell lung cancer.
Authors: Elisa Andrini, Giuseppe Lamberti, Giulia Argalia, Emilia Fortunati, Stefano Fanti, Davide Campana, Andrea Ardizzoni
Journal: Journal of Clinical Oncology (2022)

8574 Background: Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine lung cancer, accounting for 10-15% of all lung cancers, commonly classified in limited stage (LS-SCLC) and extensive stage (ES-SCLC). Despite the introduction of chemoimmunotherapy as new standard first-line therapy for ES-SCLC, the benefit of addition of the programmed-death ligand 1 (PD-L1) inhibitors is limited to a subset of patients, suggesting the importance to identify predictive biomarkers of response. [18F]FDG-PET/CT is commonly used for the staging and therapeutic planning of SCLC patients. Metabolic parameters derived from [18F]FDG-PET could predict patient outcomes by measuring the extension of metabolically active tumor (metabolic tumor volume [MTV]) or its metabolic heterogeneity (total lesion glycolysis [TLG]). Methods: We retrospectively collected patients with pathologically confirmed diagnosis of SCLC, who had undergone an [18F]FDG PET/CT scan within 30 days from the start of first-line treatment for ES-SCLC. Patients with LS-SCLC at diagnosis were included if presenting relapse at pre-treatment scans performed at least 90 days from the end of treatment with radical intent. We calculated metabolic parameters, MTV and TLG, by summing each single lesion’s MTV and TLD respectively. The primary endpoint of the study was overall survival (OS), defined as the time from [18F]FDG PET/CT scan acquisition to death from any cause. Results: A total of 86 SCLC patients ES-SCLC were included. Patients with hyponatremia, hypoalbuminemia and elevated LDH levels were associated with greater number of lesions, greater total MTV, and higher total TLG at [18F]FDG-PET/CT/CT scan. At a median follow-up of 20.9 months, the median OS was 11.1 months. Median survival was longer among patients with Na + ≥135 mEq/L, with normal albumin levels and in those with normal LDH levels and without bone metastases. Patients with low total MTV had longer OS compared with those with high total MTV (11.9 months vs 4.8 months, respectively). High total MTV was independently associated with the risk of death (p &lt; 0.001) but not with the risk of progression. Conclusions: Our preliminary data showed that total MTV could provide prognostic information in patients with ES-SCLC, suggesting a potential role as stratification factor in immunotherapy-based clinical trials.
Project BRA: Breast cancer risk assessment.
Authors: Lauren Elizabeth Nye, Sharla Smith, Catherine J Knight, Jennifer R. Klemp
Journal: Journal of Clinical Oncology (2022)

10549 Background: In Kansas, breast cancer (BC) incidence is similar in Black and white women, yet Black women are 42% more likely to die from the disease. In models where screening is equal, there is no difference in survival from early-stage BC. Barriers to BC early detection in Black women include provider lack of knowledge in cancer risk, performing risk assessments and providing culturally sensitive education to patients. Our team developed a didactic and case-based learning intervention using Project ECHO (Extension for Community Health Outcomes) to improve provider knowledge on performing BC risk assessment and enhance risk stratified screening in Community Health Clinics (CHCs). A Community Advisory Board (CAB) was established to address barriers to early detection. Methods: CHCs participated in five 1-hour ECHO sessions June thru August 2021. Session topics focused on calculating BC risk, community resources, and cultural sensitivity and were led by experts in breast oncology, risk, genetics, screening, and health care equity. Pre/post surveys administered to participants assessed knowledge and satisfaction and continuing education credits were offered. A CAB member survey gained insight into organizational characteristics and community reach. Asset mapping identified barriers, resources, and opportunities to promote BC screening. Descriptive statistical analyses and the RE-AIM framework were used to assess reach and scalability of the ECHO. Results: Seventy-seven individuals from 16 CHCs registered to participate with a mean of 26 attendees at each session and 34% attending two or more. Participants were physicians (19%), advanced practice providers (18%), nurses (29%), and allied health professionals (34%). Sixty-three (82%) completed the baseline survey and 10 (13%) completed the post-ECHO survey. At baseline, 32% of participants reported lack of training and time as barriers to performing risk assessment. While post-ECHO survey responses were low, 60% reported their knowledge greatly or moderately improved across all topics. Participants reported clinical practice change in assessing personal history of cancer and collecting family history beyond first degree relatives. CAB members reported a broad range of expertise in community engagement and development (44%), direct patient care (15%), healthcare access (15%) and patient advocacy (26%). CAB education and collaboration led to support for tomosynthesis for women screened in our state funded BC screening program, Early Detection Works (EDW). Ongoing asset mapping identified gaps in access for Black women to the EDW program. Conclusions: Project BRA demonstrated successful participation in a limited series Project ECHO and achieved perceived changes in knowledge on performing BC risk assessment. Next steps include incorporating CAB informed opportunities to expand risk-based screening across Kansas and advocate for improved access to risk stratified screening.